Amiodarone Induced Thyrotoxicosis in the Setting of End Stage Cardiomyopathy

Amiodarone is a class III antiarrhythmic agent which has effects of myocardial depolarization and repolarization. Due to its many side effects including thyroid dysfunction, its use is limited to life-threatening arrhythmias. The thyrotoxicosis can be from the iodine content of amiodarone or its direct toxicity on the thyroid gland. Because of the long half-life, causing amiodarone to have effects for months, medical management can be challenging, and thyroidectomy may be indicated. This is a 76-year-old man with a history of systolic heart failure with reduced ejection fraction (15%), on milrinone after cardiac resynchronization therapy, and recurrent ventricular tachycardia on amiodarone. He was admitted after his ICD device fired. During initial admission, his TSH was <0.015mcunit/mL and FT4 was 2.34ng/dL. Due to concern for amiodarone induced thyrotoxicosis (AIT), he was started on methimazole, prednisone, and cholestyramine. FT4 decreased from 2.34ng/dL to 2.23ng/dL and he discharged on methimazole 30mg daily and prednisone 20mg daily with plans to taper. He was seen outpatient with continued improvement in his FT4 to 2.09ng/dL. He was then seen again and found to have a rising FT4 to 2.22ng/dL and his regimen of prednisone was reinitiated at 10mg daily and methimazole increased to 40mg daily. Despite the medication changes, he continued to have an elevation in his FT4 up to 3.00ng/dL at which point he returned to the hospital for further evaluation and was given methimazole 60mg TID, prednisone 20mg daily, and restarted cholestyramine. With his significant cardiovascular risk, aggressive medical management was attempted prior to surgical evaluation. After his thyroid function failed to respond to medical intervention, multidisciplinary discussion was had with patient, family, and physician teams regarding surgical intervention versus continued long-term monitoring. Family elected to pursue surgery. Thyroidectomy was performed by an experienced endocrine surgeon successfully and his FT4 and T3 decreased appropriately requiring him to be initiated on levothyroxine supplementation. AIT can be separated into Type I, in which there is an increase in synthesis of T4 and T3 with amiodarone providing increasing substrate, and Type II in which there is destructive thyroiditis, releasing excess T4 and T3. In the United States, approximately 5% of individuals who are on amiodarone therapy develop hyperthyroidism, majority being Type II. If possible, amiodarone should be discontinued in Type I AIT, but there is no clear evidence for discontinuation in Type II. Medical management includes thionamides for Type I AIT and glucocorticoids for Type II AIT. Patients who are refractory to drug therapy should be treated with thyroidectomy. The advantages of a surgical procedure with careful cardiovascular monitoring overall outweigh the morbidity and mortality of uncontrolled thyrotoxicosis.

The effectiveness of benzbromarone versus febuxostat in gouty patients: a retrospective study

Background Benzbromarone and febuxostat have different mechanisms in reducing serum urate. Nevertheless, the effectiveness of benzbromarone versus febuxostat in reducing serum urate in gouty patients classified with different types of hyperuricemia remain unclear.Methods In this retrospective study from January 1, 2018 to September 30, 2020, subjects were retrieved if they were newly treated with benzbromarone 25mg daily or febuxostat 20mg daily with 24-hour urinary uric acid and 24-hour urinary creatinine measured. Baseline data and follow-up information after 28 ± 3 days treatment were collected from medical records. Subjects were classified into four types according to their 24-hour urinary uric acid and fractional excretion of uric acid.Results A total of 73 subjects with gout were finally enrolled. Among them, 50 were treated with benzbromarone. The percent changes in serum urate from the baseline were -33.71 ± 13.59% in benzbromarone group and -29.45 ± 10.62% in febuxostat group without significant difference between the two groups (P = 0.188). In subgroup analysis, no differences were found between the two groups among subjects classified as renal underexcretion, the combined type, or “normal” type. In patients with eGFR ≥ 70 mL/min/1.73m2, the rate of serum urate lowering was higher in those treated with benzbromarone than febuxostat. Renal function did not change significantly from the baseline for both drugs.Conclusion Benzbromarone 25mg daily and febuxostat 20mg daily had comparable effectiveness in lowering serum urate among different types of hyperuricemia. Benzbromarone was more effective than febuxostat in lowering serum urate in subjects with eGFR ≥ 70 mL/min/1.73m2.

Australian and New Zealand Registry of Anticoagulation in the Obese: Prescribing Patterns, Drug Levels and Patient Outcomes

Background: There is limited data to guide prescribing of all available anticoagulants in obese patients, in particular those weighing > 150kg or with a BMI > 40kg/m2. We aimed to examine anticoagulant prescribing patterns in obese patients in Australia and New Zealand including choice of agent and dosing, determine whether patients with obesity achieve appropriate direct oral anticoagulant (DOAC) levels and evaluate the efficacy and safety of anticoagulation in obese patients. Methods: Patients with a BMI > 35kg/m2 or weight > 120kg receiving anticoagulant therapy are prospectively identified at 7 sites in Australia and New Zealand. Demographic data, indication for anticoagulation and choice of anticoagulant are collected at baseline. At follow-up visits, drug specific levels, dose adjustments and clinical progress (symptoms, imaging, recurrent thrombosis and adverse events) are recorded. Results: 155 patients have been recruited across seven sites (recruitment ongoing). The median age of patients was 53 (range 22-85) and 49% of patients were male. 77 (50%) of patients were anticoagulated for pulmonary embolus (PE) while 40% were anticoagulated for deep vein thrombosis (DVT) without PE. Initial anticoagulant prescribed was apixaban in 37 patients, dabigatran in 4 patients, rivaroxaban in 57 patients, low molecular weight heparin (LMWH) in 29 patients and warfarin in 28 patients (Table 1). A subset of patients initially received LMWH for 5-14 days prior to transition to a DOAC (rivaroxaban in 7, dabigatran in 6). There was cross-over between agents during the study period. Table 2 demonstrates median peak and trough DOAC levels. All peak apixaban levels and 25 of 37 (68%) peak rivaroxaban levels were within the therapeutic ranges published by the International Council for Standardization in Haematology (Gosselin, Thromb Haemost. 2018). Assessment of appropriate trough levels was limited by the limit of detection at different laboratories. 27 patients receiving enoxaparin had at least one peak Anti-Xa level (target peak 0.5-1.2U/ml). The median enoxaparin dose to achieve therapeutic peak Anti-Xa was 0.9mg/kg (range 0.52-1.3). 15 patients weighing > 150kg had a recorded peak Anti-Xa, 10 of these patients were prescribed a capped dose of 150mg BD (weight range 155-290kg) and nine had a therapeutic Anti-Xa and one had a supratherapeutic Anti-Xa measurement. One patient had a PE on apixaban 5mg twice daily (in the setting of suspected non-compliance), one patient had a new confirmed PE after 4 days of non-compliance with rivaroxaban 20mg daily and another patient had a confirmed recurrence on therapeutic warfarin. 1 patient had a PE when warfarin was withheld for emergency surgery. An equivocal recurrence occurred on enoxaparin with a supratherapeutic Anti-Xa (1.76 U.ml) and 1 DVT occurred on dabigatran for a cardiac indication (no drug level available). One patient had recurrent superficial thrombophlebitis on rivaroxaban 20mg daily (peak 301ng/L and trough <30ng/L). There was one episode of life-threatening gastrointestinal bleeding on dabigatran. Conclusion: There is limited data to guide prescribing of all anticoagulants in obese patients, in particular in patients weighing > 150kg or BMI > 40kg/m2. There is increasing use of DOACs in Australia and New Zealand in patients with obesity given the ease of administration and lack of monitoring required. Despite the recommendation to perform DOAC levels in this group of patients, interpretation of levels is difficult due to a lack of well validated therapeutic ranges with clinical correlation. Further data regarding the clinical utility of DOAC levels, appropriate dosing strategy for enoxaparin, and clinical outcomes in this population is required. Our registry provides data regarding drug levels in this population, prescribing characteristics and clinical outcome data. Disclosures No relevant conflicts of interest to declare.

A phase I/Ib study of lenvatinib and cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

6541 Background: Despite overexpression of EGFR in HNSCC, cetuximab monotherapy has limited benefit. Fibroblast growth factor receptor (FGFR) signaling is a known resistance mechanism to EGFR inhibition. Lenvatinib is a multi-targeted receptor tyrosine kinase inhibitor (RTKI) and has unique activity against FGFR 1,2,3, and 4. We are evaluating inhibition of EGFR and RTKs including FGFR through the combination of cetuximab and lenvatinib in patients (pts) with R/M HNSCC. Methods: In this phase I/Ib, single-institution study, pts with measurable disease per RECIST v1.1 that is incurable with surgery and radiation are eligible regardless of prior cetuximab therapy. The dose de-escalation phase included pts with HNSCC and cutaneous squamous cell carcinoma (cSCC) treated with standard cetuximab dosing and lenvatinib in 3 potential dose levels (DL): (0) 24mg, (-1) 20mg, (-2) 14mg oral daily in a standard 3+3 design. The primary objective was to determine the MTD of lenvatinib in combination with cetuximab. The expansion phase included an additional 5 pts with HNSCC treated at the MTD. Exploratory endpoints include ORR and PFS in HNSCC pts treated at the MTD. Results: 12 evaluable pts were treated on the dose de-escalation phase. There were no DLTs on DL 0; however, 3/6 pts were removed immediately following the 28-day DLT period due to toxicity that included extensive thrombotic events and athlerosclerotic disease. On DL -1, 0/6 pts (5 HNSCC/1 cSCC) had a DLT establishing lenvatinib 20mg daily as the MTD. 7 pts were enrolled onto the expansion phase; 4 are currently evaluable for response and 2 are unevaluable because of withdrawal due to a cetuximab reaction and required surgery. Of the 9 evaluable HNSCC pts treated with lenvatinib 20mg daily, 6 pts had a PR with a 67% ORR. For the 8 pts who have completed treatment, the median PFS is 3.6 months (range 1.6-10.4). Grade 3 AEs regardless of attribution included hypertension (3), oral mucositis (3) and oral cavity fistula (1). The most common AEs were acneiform rash (7), fatigue (6), and hypertension/hypothyroidism/oral mucositis (5 each). Conclusions: The MTD of lenvatinib 20mg daily with cetuximab appears to be active in R/M HSNCC with an impressive preliminary ORR, warranting further evaluation of the efficacy of this combination. Clinical trial information: NCT03524326 .

Blistering eruptions following isotretinoin therapy for hidradenitis suppurativa: a case report

A 33-year-old male was treated with isotretinoin (20mg daily) for hidradenitis suppurativa. After 6 weeks on the medication, he developed symmetrical erythematous tense blisters on the lower legs. Report of biopsy done was of intraepidermal blisters with superficial dermal lymphohistiocytic infitrates. He was commenced on oral prednisolone 30mg daily and Isotretinoin was withdrawn. The blisters resolved over a 2week period. The lesions of hidradenitis suppurativa were noticed to have improved with the short course of isotretionoin.

Antimicrobial Effectiveness of Chlorhexidine Chewing Gums on Streptococcus Mutans Counts– An in vivo Microbiological Study

The aim of the present study was to evaluate the antimicrobial efficacy of Chlorhexidine chewing gums and to assess the effect of dosage and frequency of intake of Chlorhexidine gums on Streptococcus mutans(SM)count. Method: The sample consisted of 30 subjects, divided into two groups AI & AII. Each group consisted of 15 subjects. Group AI chewed 2 Chlorhexidine Chewing gum X Twice Daily for 20 minutes (Total = 4 gums Daily) & Group AII chewed 2 Chlorhexidine Chewing gum X Four times daily for 20 minutes (Total= 8 gums Daily) & saliva sample was collected & agar plates were inoculated for SM colony count. The study was carried for a week's time and salivary sample collected were Baseline, Day 1 morning and evening, Day 4 evening, Day7 morning and evening. Results: After the gum was chewed, it was observed that the colony count started to decrease when compared with baseline in both the groups. The fall in SM count was statistically highly significant with p < 0.001 in both the groups. When comparing between Group AI (Dosage 20mg daily) and Group AII (Dosage 40mg daily), the fall in SM count for both the groups was not statistically significant with p-value > 0.05. It was concluded that there was reduction in the level of Salivary SM, but was not statistically significant, by increasing the dosage and frequency of intake of Chlorhexidine containing gums. Conclusions: We recommend that dosage of Chlorhexidine containing chewing gums can be restricted to four gums instead of eight gums per day.